MACROPHAGE CONTROL OF NORMAL AND LEUKEMIC ERYTHROPOIESIS

Project Details

Description

Studies in our laboratory have demonstrated that macrophages can directly
affect erythropoiesis, both in vitro and in vivo. Using a unique model
system developed in our laboratory, we have found that this macrophage
regulation of erythropoiesis is impaired in leukemia. Regulation can be
restored and the leukemia reversed by the treatment of fully leukemic
animals with normal macrophages.

When macrophages are transferred to normal or leukemic animals, erythroid
colony formation (CFU-E) is significantly suppressed. The data suggest
that macrophages do not suppress erythropoiesis in vivo through regulation
of EPO levels but by an influence on novel erythropoietic stimulatory
factor. This factor is produced in response to anemic stress and is
present in impure but not purified preparations of EPO. The factor can be
measured by its ability to reverse macrophage suppression of CFU-E and has
no activity in the traditional in vivo standard plasma EPO assay.
Preliminary characterization reveals that the activity is a glycoprotein of
approximately 40,000 daltons.

No suppressive activity has been detected by normal macrophages in vitro.
The production in vitro of a CFU-E stimulatory factor by virus-infected
macrophages correlates with the failure of leukemic animals to experience
regression.

Our goals for the coming year are to: (1) extend our present studies to
include isolation and characterization of the factor related to EPO that
appears to be regulated either directly or indirectly by normal
macrophages; (2) determine the factor's role in vivo in regulation of
erythropoiesis; and (3) characterize the in vitro stimulatory factor
produced by virus-infected macrophages. (MB)
StatusFinished
Effective start/end date12/31/891/1/90

Funding

  • National Cancer Institute
  • National Cancer Institute
  • National Cancer Institute
  • National Cancer Institute

ASJC

  • Cancer Research

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